title: The growth of glioblastoma orthotopic xenografts in nude mice is directly correlated with impaired object recognition memory.
abstract: Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18days (D9, D14, and D18, respectively) after implantation of 5×10(5) cells. At D9, the mice showed normal behavior when tested 90min or 24h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors.
authors.affiliation: International Research Center, A.C. Camargo Cancer Center, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Wasilewska-Sampaio
authors.forename: Tiago G
authors.initials: TG
authors.lastname: Santos
authors.forename: Marilene Hohmuth
authors.initials: MH
authors.lastname: Lopes
authors.forename: Martin
authors.initials: M
authors.lastname: Cammarota
authors.forename: Vilma Regina
authors.initials: VR
authors.lastname: Martins
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000150:complications* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D021641:Recognition, Psychology / Q000502:physiology*; D013223:Statistics as Topic; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods
keywords: Behavior; Glioblastoma; Nude mice; Tumor growth; Xenografts